The DOI matches its Crossref record; 18 of the 18 references it cites were found in a registry or an index.
Mitochondrial Alterations in PINK1 Deficient Cells Are Influenced by Calcineurin-Dependent Dephosphorylation of Dynamin-Related Protein 1
Open accessAbstract
PTEN-induced novel kinase 1 (PINK1) mutations are associated with autosomal recessive parkinsonism. Previous studies have shown that PINK1 influences both mitochondrial function and morphology although it is not clearly established which of these are primary events and which are secondary. Here, we describe a novel mechanism linking mitochondrial dysfunction and alterations in mitochondrial morphology related to PINK1. Cell lines were generated by stably transducing human dopaminergic M17 cells with lentiviral constructs that increased or knocked down PINK1. As in previous studies, PINK1 deficient cells have lower mitochondrial membrane potential and are more sensitive to the toxic effects of mitochondrial complex I inhibitors. We also show that wild-type PINK1, but not recessive mutant or kinase dead versions, protects against rotenone-induced mitochondrial fragmentation whereas PINK1 deficient cells show lower mitochondrial connectivity. Expression of dynamin-related protein 1 (Drp1) exaggerates PINK1 deficiency phenotypes and Drp1 RNAi rescues them. We also show that Drp1 is dephosphorylated in PINK1 deficient cells due to activation of the calcium-dependent phosphatase calcineurin. Accordingly, the calcineurin inhibitor FK506 blocks both Drp1 dephosphorylation and loss of mitochondrial integrity in PINK1 deficient cells but does not fully rescue mitochondrial membrane potential. We propose that alterations in mitochondrial connectivity in this system are secondary to functional effects on mitochondrial membrane potential.
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Citations
Cites
Parkin is recruited selectively to impaired mitochondria and promotes their autophagy
Narendra, D., Tanaka, A., Suen, D.-F., & Youle, R. J. (2008) · The Journal of Cell Biology · doi:10.1083/jcb.200809125 · Cited by 4,026
Hereditary Early-Onset Parkinson's Disease Caused by Mutations in PINK1
Valente, E. M., Abou-Sleiman, P. M., Caputo, V., Muqit, M. M. K., Harvey, K., Gispert, S., Ali, Z., Del Turco, D., Bentivoglio, A. R., Healy, D. G., et al. (2004) · Science · doi:10.1126/science.1096284 · Cited by 3,481
Fission and selective fusion govern mitochondrial segregation and elimination by autophagy
Twig, G., Elorza, A., Molina, A. J. A., Mohamed, H., Wikstrom, J. D., Walzer, G., Stiles, L., Haigh, S. E., Katz, S., Las, G., et al. (2008) · The EMBO Journal · doi:10.1038/sj.emboj.7601963 · Cited by 3,082 · cited 1×
“The dynamic regulation of mitochondrial morphology is important in maintaining the health of the organelle and of the cell [25,45,46].”
BackgroundMitofusin 2 tethers endoplasmic reticulum to mitochondria
de Brito, O. M., & Scorrano, L. (2008) · Nature · doi:10.1038/nature07534 · Cited by 2,442
Drosophila pink1 is required for mitochondrial function and interacts genetically with parkin
Clark, I. E., Dodson, M. W., Jiang, C., Cao, J. H., Huh, J. R., Seol, J. H., Yoo, S. J., Hay, B. A., & Guo, M. (2006) · Nature · doi:10.1038/nature04779 · Cited by 1,788
Mitochondrial dysfunction in Drosophila PINK1 mutants is complemented by parkin
Park, J., Lee, S. B., Lee, S., Kim, Y., Song, S., Kim, S., Bae, E., Kim, J., Shong, M., Kim, J.-M., et al. (2006) · Nature · doi:10.1038/nature04788 · Cited by 1,705
Functions and dysfunctions of mitochondrial dynamics
Detmer, S. A., & Chan, D. C. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2275 · Cited by 1,369
Mitotic phosphorylation of dynamin-related GTPase Drp1 participates in mitochondrial fission.
Taguchi, N., Ishihara, N., Jofuku, A., Oka, T., & Mihara, K. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m607279200 · Cited by 1,226
Dephosphorylation by calcineurin regulates translocation of Drp1 to mitochondria
Cereghetti, G. M., Stangherlin, A., de Brito, O. M., Chang, C. R., Blackstone, C., Bernardi, P., & Scorrano, L. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0808249105 · Cited by 1,129
The PINK1/Parkin pathway regulates mitochondrial morphology
Poole, A. C., Thomas, R. E., Andrews, L. A., McBride, H. M., Whitworth, A. J., & Pallanck, L. J. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0709336105 · Cited by 885
Cited by
PINK1 Is Selectively Stabilized on Impaired Mitochondria to Activate Parkin
Narendra, D. P., Jin, S. M., Tanaka, A., Suen, D.-F., Gautier, C. A., Shen, J., Cookson, M. R., & Youle, R. J. (2010) · PLoS Biology · doi:10.1371/journal.pbio.1000298 · Cited by 2,944
Self-citationThe Role of Oxidative Stress in Parkinson's Disease
Dias, V., Junn, E., & Mouradian, M. M. (2013) · Journal of Parkinson’s Disease · doi:10.3233/jpd-130230 · Cited by 1,845
Proteasome and p97 mediate mitophagy and degradation of mitofusins induced by Parkin
Tanaka, A., Cleland, M. M., Xu, S., Narendra, D. P., Suen, D.-F., Karbowski, M., & Youle, R. J. (2010) · Journal of Cell Biology · doi:10.1083/jcb.201007013 · Cited by 1,369
“First, immediately after depolarization, 1377PINK1- and Parkin-mediated proteasomal degradation of Mfn1 and Mfn2 • Tanaka et al. (Exner et al., 2007; Dagda et al., 2009; Lutz et al., 2009; Sandebring et al., 2009).”
BackgroundGegg, M. E., Cooper, J. M., Chau, K.-Y., Rojo, M., Schapira, A. H. V., & Taanman, J.-W. (2010) · Human Molecular Genetics · doi:10.1093/hmg/ddq419 · Cited by 910
The Interplay Between Mitochondrial Dynamics and Mitophagy
Twig, G., & Shirihai, O. S. (2011) · Antioxidants & Redox Signaling · doi:10.1089/ars.2010.3779 · Cited by 778
Metadata
- Authors
- Sandebring, A., Thomas, K. J., Beilina, A., van der Brug, M., Cleland, M. M., Ahmad, R., Miller, D. W., Zambrano, I., Cowburn, R. F., Behbahani, H., Cedazo-Mínguez, A., & Cookson, M. R.
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2009-05-27
- Volume
- 4
- Issue
- 5
- Pages
- e5701
- ISSN
- 1932-6203 (ISSN-L)
- OpenAlex
- W2048621445
- Cited by
- 176
- References
- 18
- FWCI
- 11.16
- Type
- journal article
- Language
- en
- Open access
- gold
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- Sandebring, A., Thomas, K. J., Beilina, A., van der Brug, M., Cleland, M. M., Ahmad, R., Miller, D. W., Zambrano, I., Cowburn, R. F., Behbahani, H., Cedazo-Mínguez, A., & Cookson, M. R. (2009). Mitochondrial Alterations in PINK1 Deficient Cells Are Influenced by Calcineurin-Dependent Dephosphorylation of Dynamin-Related Protein 1. PLoS ONE. https://doi.org/10.1371/journal.pone.0005701
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